A recent analysis showed that although age-adjusted US rates of cutaneous T-cell lymphoma (CTCL) incidence rose between 2000 and 2015, the number of cases declined from 2015 to 2022 — a timeframe marked by widespread use of biologic drugs that have raised concerns about potentially inducing or exacerbating CTCL. As an epidemiologic study, the analysis did not assess causality. However, authors and a CTCL expert agreed that it is plausible that dupilumab in particular might have accounted for at least some of the downturn.

The study was published online last month as a brief report in the Journal of the American Academy of Dermatology. 

“The main findings surprised us,” senior author Larisa J. Geskin, MD, told Medscape Dermatology. Geskin is a professor of dermatology (in medicine) and director of the Comprehensive Skin Cancer Center at Columbia University Medical Center in New York City.

Historically, Geskin said, studies have consistently reported rising CTCL incidence over time. Although many previous studies used short observation periods or smaller datasets, she said, the most directly comparable prior study included 14,942 patients from the Surveillance, Epidemiology, and End Results (SEER) database and shows that from 2000 to 2018, overall age-adjusted CTCL incidence increased 0.61% annually.

To determine whether reported increases have continued and whether trends differ depending on CTCL subtype and sociodemographic factors, Geskin and colleagues queried the SEER-21 registry, which includes approximately 46% of the US population. This analysis yielded 24,988 histologically confirmed malignant CTCL cases with a primary cutaneous site reported between 2000 and 2022. Parallelism testing with Joinpoint v5.4.0.0 software identified 2015 as the juncture where overall incidence trajectory shifted — from +1.65% to –2.86% annually post-2015. 

“Joinpoint regression fits trend lines to incidence rates over time and statistically identifies where the trend significantly changes,” said first author Joshua A. Kent, BA, a dermatology research fellow at Columbia University Medical Center and a medical student at the State University of New York at Buffalo. 

Incidence rates for many common CTCL subtypes mirrored the overall trajectory, with 2015-2022 reductions between 1.20% (mycosis fungoides) and 15.04% (peripheral T-cell lymphoma not otherwise specified) annually. Conversely, incidence rates for Sézary syndrome rose 4.2% throughout the study, while rates of primary cutaneous T-cell lymphoma not otherwise specified declined continuously. Additionally, parallelism testing showed the greatest post-2015 reductions among non-Hispanic White patients, patients at least 40 years old, and patients in areas of higher socioeconomic status.

Dupilumab and Other Biologics 

The study’s findings are clinically relevant, said Geskin, because the past several years have witnessed growing concern about CTCL being diagnosed in patients receiving biologic therapies — particularly dupilumab for atopic dermatitis (AD). “Numerous case reports have appeared,” she added, “and understandably this has raised the question of whether these drugs might actually cause or accelerate lymphoma.” 

SEER data do not capture individual medication exposures, said Geskin, and the study does not prove that biologics are protective. “But at the population level,” she told Medscape Dermatology, “we are seeing the opposite of what one might expect if widespread biologic use were producing a meaningful increase in CTCL.”

For practicing dermatologists, Geskin said, the foregoing distinction is important because a CTCL diagnosis occurring after a patient receives dupilumab does not establish that the drug caused the lymphoma. “Early mycosis fungoides can be extraordinarily difficult to distinguish, clinically and histologically, from eczema or psoriasis,” she said, “and patients may carry an inflammatory diagnosis for years before CTCL is recognized.”

Moreover, said Geskin, many published cases lacked rigorous molecular evaluation to establish whether CTCL was present before biologic exposure. Kent noted that a systematic review identified 27 patients across 12 studies and highlighted frequent diagnostic difficulties, including negative or equivocal T-cell receptor studies. 

“Therefore,” Geskin said, “one very plausible explanation for at least some of these cases is unmasking of previously unrecognized CTCL rather than induction of a new lymphoma.”

Other existing studies lend mechanistic plausibility to the hypotheses that dupilumab may protect against CTCL development. Specifically, studies published by Geskin’s team in 2015 and in 2025, respectively, showed that interleukin (IL)-13 regulates CTCL proliferation, and that blocking IL-4/IL-13 suppresses malignant T-cell proliferation and promotes anti-tumor immunity. Because the present study’s design precluded distinguishing whether biologics targeting IL-17 also might have accounted for CTCL declines, however, Geskin cautioned against overinterpreting the authors’ findings. 

“The importance of this study is that it identifies a signal and generates a hypothesis that can now be tested properly,” she said. “We need longitudinal studies that link biologic exposure with CTCL outcomes at the individual patient level.” 

Unexplained Decline

Based on prior publications, said Patrick Brunner, MD, MSc, the dermatology community has long been under the impression that CTCL incidence is constantly increasing. Brunner, professor of dermatology and vice chair of research at the Icahn School of Medicine at Mount Sinai in New York City, was not involved with the study but was asked to comment on the findings.

“Then there’s this surprising decline after 2015 that essentially remains unexplained,” he told Medscape Dermatology. “It’s particularly interesting in light of the recent discussion regarding whether certain biologics, particularly dupilumab, would induce cutaneous lymphomas. It’s a controversy and a highly debated question in the field.” 

In the study, Brunner said, the appearance of the downturn right around when dupilumab gained widespread use places the argument in a new light. “So it’s a very important paper,” he said, “and I’m sure it’s going to cause many more discussions at scientific meetings and in scientific literature.”

The potential for IL-4/IL-13 blockade to reduce CTCL incidence as described by Geskin and colleagues is “absolutely possible,” added Brunner, who is also director of the Cutaneous Lymphoma Clinic at Mount Sinai. Another possibility, which authors acknowledged, is that high-throughput sequencing of T-cell receptor rearrangements could be cutting the number of false-positive CTCL diagnoses. 

For any dermatologist who treats AD, said Brunner, the study adds a novel, important facet to the discussion regarding whether current targeted treatments can worsen or even cause lymphomas. Beyond the clinic, he added, the study will be “a very important instigator of further research” into potential causes for the observed decline.

Geskin has been an investigator for Johnson & Johnson, Mallinckrodt, Kyowa Kirin, Soligenix, Innate Pharma, Incyte, Trillium Therapeutics, Merck, Bristol Myers Squibb, and Stratpharma; and a scientific advisor for SciTech Development and Citius Pharmaceuticals. Kent reports no relevant financial relationships. 

Brunner has been a consultant, speaker, and/or investigator for AbbVie, Pfizer, and UCB; has received consulting and/or speaker honoraria and fees from Almirall, Sanofi, Janssen, LEO Pharma, Boehringer Ingelheim, GSK, Regeneron, Eli Lilly, Celgene, Novartis, Merck, RAPT Therapeutics, Galderma, Immunocore, Apogee Therapeutics, Incyte, and Bristol Myers Squibb; has provided legal consulting for product liability defendants in cases involving dupilumab; and is an investigator for Nektar Therapeutics. 

John Jesitus is a Denver-based freelance medical writer and editor.